tbuckley/cabot-search huggingface dataset:
A dendritic/tumor fusion cell vaccine enhances efficacy of nanobody-based CAR-T cells against solid tumor
Authors: Shuyang Sun, Ziqiang Ding, Li Gao, Bruce D. Hammock, Xianing Huang, Zhi Ping Xu, Xuan Wang, Qihong Cheng, Fengzhen Mo, Wei Shi, Shenxia Xie, Aiqun Liu, Haixia Li, Xiaomei Yang, Xiaoling Lu
Journal: Theranostics (2023)

Background: Chimeric antigen receptor (CAR) T-cell therapy is practical in treating cancers of hematopoietic origin, but of that in solid tumors compromises efficacy for the loss of the antigen recognized by the CAR. However, dendritic cell (DC)/tumor fusion vaccines present a spectrum of known or unknown tumor antigens to stimulate T cell expansion and enhanced T cell response. Developing a new strategy of enhanced nanobody-based CAR-T (Nb-CAR-T) cells antitumor activity by DC/tumor fusion vaccines stimulation would provide guidance for more effective CAR-T cell therapies. Methods: Considering the therapeutic potential of nanobody (Nb), we first screened EGFRvIII Nb, then constructed and verified the function of EGFRvIII Nb-CAR-T cells in vitro and in vivo. We further combined DC/tumor fusion vaccines to boost EGFRvIII Nb-CAR-T cells antitumor effect, which was evaluated in vitro Nb-CAR-T cell function and in the tumor-bearing xenograft mouse models. Results: We had for the first time successfully selected EGFRvIII Nb for the generation of the novel EGFRvIII Nb-CAR-T cells. Importantly, our results suggested that DC/tumor fusion vaccines stimulate Nb-CAR-T cells response not only in improving T cell proliferation, T cell activation, cytokine secretion and tumor-specific cytotoxicity in vitro, but also significantly reducing tumor burden, prolonging survival and improving Nb-CAR-T cells infiltration. Conclusions: We have innovatively shown that DC/tumor fusion vaccines significantly enhance the efficacy of Nb-CAR-T cells against solid tumors. This new strategy has provided a promising therapeutic platform for promoting the clinical treatment of CAR-T cells therapy.
Oral [60]fullerene reduces neuroinflammation to alleviate Parkinson's disease via regulating gut microbiome
Authors: Xue Li, Ruijun Deng, Jie Li, Hui Li, Zhe Xu, Lei Zhang, Linyin Feng, Chunying Shu, Mingming Zhen, Chunru Wang
Journal: Theranostics (2023)

Neuroinflammation is considered to drive the pathogenic process of neuronal degeneration in Parkinson's disease (PD).However, effective anti-neuroinflammation therapeutics for PD still remain dissatisfactory.Here we explore a robust therapeutic strategy for PD using anti-neuroinflammatory fullerenes.Methods: Oral fullerene was prepared by a ball-milling method.1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP)-induced PD mouse model was used to investigate the therapeutic effects and mechanisms of it.The gut microenvironment was evaluated by 16S rRNA gene sequencing, gas chromatography-mass spectrometry, quantitative polymerase chain reaction (Q-PCR), and western blot (WB).The neuroinflammation and neurodegeneration were evaluated by pathological analysis, Elisa kits, transmission electron microscopy, Q-PCR, WB and so on.Toxicity was assessed by weight, blood test and hematoxylin-eosin (HE) staining.Results: Oral fullerene therapeutic system that dissolved [60]fullerene into olive oil (abbreviated as OFO) was dexterously designed, which could reduce neuroinflammation via regulating the diversity of gut microbiome, increasing the contents of short chain fatty acids (SCFAs) and recovering the integrity of gut barrier.Accordingly, the reduction of neuroinflammation prevented dopaminergic neuronal degeneration.And thus, OFO significantly ameliorated motor deficits and fundamentally reversed dopamine (DA) loss in MPTP-induced PD mice.Of note, OFO exhibited low toxicity towards the living body.Conclusion: Our findings suggest that OFO is a safe-to-use, easy-to-apply, and prospective candidate for PD treatment in clinic, opening a therapeutic window for neuroinflammation-triggered neurodegeneration.
Chinese herb pollen derived micromotors as active oral drug delivery system for gastric ulcer treatment
Authors: Lijun Cai, Cheng Zhao, Xinyue Cao, Minhui Lu, Ning Li, Yuan Luo, Yongan Wang, Yuanjin Zhao
Journal: Bioactive Materials (2023)

Considerable efforts have been devoted to treating gastric ulcers. Attempts in this field tend to develop drug delivery systems with prolonged gastric retention time. Herein, we develop novel Chinese herb pollen-derived micromotors as active oral drug delivery system for treating gastric ulcer. Such Chinese herb pollen-derived micromotors are simply produced by asymmetrically sputtering Mg layer onto one side of pollen grains. When exposed to gastric juice, the Mg layer can react with the hydrogen ions, resulting in intensive generation of hydrogen bubbles to propel the micromotors. Benefiting from the autonomous motion and unique spiny structure, our micromotors can move actively in the stomach and adhere to the surrounding tissues. Besides, their special architecture endows the micromotors with salient capacity of drug loading and releasing. Based on these features, we have demonstrated that our Chinese herb pollen-derived micromotors could effective deliver berberine hydrochloride and show desirable curative effect on the gastric ulcer model of mice. Therefore, these Chinese herb pollen-derived micromotors are anticipated to serve as promising oral drug delivery carriers for clinical applications.
Cascade testing for hereditary cancer: comprehensive multigene panels identify unexpected actionable findings in relatives
Authors: Brandie Heald, Sara Pirzadeh-Miller, Rachel E Ellsworth, Sarah M Nielsen, Emily M Russell, Peter Beitsch, Edward D Esplin, Robert L Nussbaum, Daniel E Pineda-Alvarez, Allison W Kurian, Heather Hampel
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Current guidelines recommend single variant testing in relatives of patients with known pathogenic or likely pathogenic germline variants in cancer predisposition genes. This approach may preclude the use of risk-reducing strategies in family members who have pathogenic or likely pathogenic germline variants in other cancer predisposition genes. Cascade testing using multigene panels was performed in 3696 relatives of 7433 probands. Unexpected pathogenic or likely pathogenic germline variants were identified in 230 (6.2%) relatives, including 144 who were negative for the familial pathogenic or likely pathogenic variant but positive for a pathogenic or likely pathogenic variant in a different gene than the proband and 74 who tested positive for the familial pathogenic or likely pathogenic variant and had an additional pathogenic or likely pathogenic variant in a different gene than the proband. Of the relatives with unexpected pathogenic or likely pathogenic germline variants, 36.3% would have qualified for different or additional cancer screening recommendations. Limiting cascade testing to only the familial pathogenic or likely pathogenic variant would have resulted in missed, actionable findings for a subset of relatives.
A machine learning-based score for precise echocardiographic assessment of cardiac remodelling in hypertensive young adults
Authors: Maryam Alsharqi, Winok Lapidaire, Yasser Iturria-Medina, Zhaohan Xiong, Wilby Williamson, Afifah Mohamed, Cheryl M J Tan, Jamie Kitt, Holger Burchert, Andrew Fletcher, Polly Whitworth, Adam J Lewandowski, Paul Leeson
Journal:  (2023)

Abstract Aims Accurate staging of hypertension-related cardiac changes, before the development of significant left ventricular hypertrophy, could help guide early prevention advice. We evaluated whether a novel semi-supervised machine learning approach could generate a clinically meaningful summary score of cardiac remodelling in hypertension. Methods and results A contrastive trajectories inference approach was applied to data collected from three UK studies of young adults. Low-dimensional variance was identified in 66 echocardiography variables from participants with hypertension (systolic ≥160 mmHg) relative to a normotensive group (systolic &amp;lt; 120 mmHg) using a contrasted principal component analysis. A minimum spanning tree was constructed to derive a normalized score for each individual reflecting extent of cardiac remodelling between zero (health) and one (disease). Model stability and clinical interpretability were evaluated as well as modifiability in response to a 16-week exercise intervention. A total of 411 young adults (29 ± 6 years) were included in the analysis, and, after contrastive dimensionality reduction, 21 variables characterized &amp;gt;80% of data variance. Repeated scores for an individual in cross-validation were stable (root mean squared deviation = 0.1 ± 0.002) with good differentiation of normotensive and hypertensive individuals (area under the receiver operating characteristics 0.98). The derived score followed expected hypertension-related patterns in individual cardiac parameters at baseline and reduced after exercise, proportional to intervention compliance (P = 0.04) and improvement in ventilatory threshold (P = 0.01). Conclusion A quantitative score that summarizes hypertension-related cardiac remodelling in young adults can be generated from a computational model. This score might allow more personalized early prevention advice, but further evaluation of clinical applicability is required.
Possible relation of cathepsin C activity and seasonal fluctuation of skin lesions in Papillon–Lefèvre syndrome
Authors: Akari Sakai, Satoru Shinkuma, Nobuaki Miura, Tokiko Deguchi, Mahoko Oginezawa, Mami Nakajima, Tatsuya Katsumi, Ryota Hayashi, Riichiro Abe
Journal: British Journal of Dermatology (2023)

Our patient with Papillon–Lefèvre syndrome with a novel p.G430V and recurrent p.G301S missense mutation showing aggravation of skin lesions in wintertime. A temperature-dependent cathepsin C enzymatic activity study indicates a possible association between seasonal fluctuations, minimal dental involvement and temperature.
Toward biologically plausible artificial vision
Authors: Mason Westfall
Journal: Behavioral and Brain Sciences (2023)

Abstract Quilty-Dunn et al. argue that deep convolutional neural networks (DCNNs) optimized for image classification exemplify structural disanalogies to human vision. A different kind of artificial vision – found in reinforcement-learning agents navigating artificial three-dimensional environments – can be expected to be more human-like. Recent work suggests that language-like representations substantially improves these agents’ performance, lending some indirect support to the language-of-thought hypothesis (LoTH).
Continued Opioid Use and Adverse Events Following Provision of Opioids for Musculoskeletal Pain in the Emergency Department: A Systematic Review and Meta-Analysis
Authors: Qiuzhe Chen, Chris G. Maher, Christopher S. Han, Christina Abdel Shaheed, Chung-Wei Christine Lin, Eileen M. Rogan, Gustavo C. Machado
Journal: Drugs (2023)

The prevalence of continued opioid use or serious adverse events (SAEs) following opioid therapy in the emergency department (ED) for musculoskeletal pain is unclear. The aim of this review was to examine the prevalence of continued opioid use and serious adverse events (SAEs) following the provision of opioids for musculoskeletal pain in the emergency department (ED) or at discharge.Records were searched from MEDLINE, EMBASE and CINAHL from inception to 7 October 2022. We included randomised controlled trials and observational studies enrolling adult patients with musculoskeletal pain who were administered and/or prescribed opioids in the ED. Continued opioid use and opioid misuse data after day 4 since ED discharge were extracted. Adverse events were coded using the Common Terminology Criteria for Adverse Events (CTCAE), and those rated as grades 3-4 (severe or life-threatening) and grade 5 (death) were considered SAEs. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool.Seventy-two studies were included. Among opioid-naïve patients who received an opioid prescription, 6.8-7.0% reported recent opioid use at 3-12 months after discharge, 4.4% filled ≥ 5 opioid prescriptions and 3.1% filled > 90-day supply of opioids within 6 months. The prevalence of SAEs was 0.02% [95% confidence interval (CI) 0, 0.2%] in the ED and 0.1% (95% CI 0, 1.5%) within 2 days. One study observed 42.9% of patients misused opioids within 30 days after discharge.Around 7% of opioid-naïve patients with musculoskeletal pain receiving opioid therapy continue opioid use at 3-12 months after ED discharge. SAEs following ED administration of an opioid were uncommon; however, studies only monitored patients for 2 days.10.31219/osf.io/w4z3u.
Primary Care Practitioner Perspectives on the Role of Primary Care in Dementia Diagnosis and Care
Authors: Alissa Bernstein Sideman, Melissa Ma, Alma Hernandez de Jesus, Cecilia Alagappan, Na’amah Razon, Daniel Dohan, Anna Chodos, Tala Al-Rousan, Loren I. Alving, Freddi Segal-Gidan, Howie Rosen, Katherine P. Rankin, Katherine L. Possin, Soo Borson
Journal: JAMA Network Open (2023)

Although the barriers to dementia care in primary care are well characterized, primary care practitioner (PCP) perspectives could be used to support the design of values-aligned dementia care pathways that strengthen the role of primary care.
Errors in Abstract and Table 3
Journal: JAMA Network Open (2023)

Xiangui He, PhD; Jingjing Wang, PhD; Zhuoting Zhu, PhD; Kaidi Xiang, MD; Xinzi Zhang, MD; Bo Zhang, MS; Jun Chen, PhD; Jinliuxing Yang, PhD; Linlin Du, MPH; Chunjin Niu, BS; Mei Leng, BS; Jiannan Huang, PhD; Kun Liu, MD; Haidong Zou, MD; Mingguang He, PhD; Xun Xu, MD
Is evidence of language-like properties evidence of a language-of-thought architecture?
Authors: Nuhu Osman Attah, Edouard Machery
Journal: Behavioral and Brain Sciences (2023)

Abstract We argue that Quilty-Dunn et al.'s commitment to representational pluralism undermines their case for the language-of-thought hypothesis as the evidence they present is consistent with the operation of the other representational formats that they are willing to accept.
The language of tactile thought
Authors: Tony Cheng
Journal: Behavioral and Brain Sciences (2023)

Abstract The target article argues that language-of-thought hypothesis (LoTH) is applicable to various domains, including perception. However, it focusses exclusively on the visual case, which is limited in this regard. I argue for two ideas in this commentary: first, their case can be extended to other modalities such as touch; and second, the status of those six criteria needs to be further clarified.
A survey-based study on experiences with and perspectives toward medical providers among patients with hidradenitis suppurativa
Authors: Diana G Marquez, Nakisa B Sadeghi, Linnea L Westerkam, Franklin R Blum, Angela Dresselhaus, Christopher J Sayed
Journal: British Journal of Dermatology (2023)

Patients with hidradenitis suppurativa frequently visit medical providers and are often misdiagnosed or inappropriately educated on their disease. This survey study investigated how often patients received misinformation about their disease. Many participants reported receiving incorrect information that caused shame and made them avoid seeing medical providers.
Benefit of skin surgical revision in high-risk basal cell carcinoma according to histopathological margins
Authors: Bénédicte Reynaud, Julien Jacquemus, Sylvie Chabaud, Yaelle Ouldbey, Sophie Darnis, Mona Amini-Adle
Journal: British Journal of Dermatology (2023)

This article investigated the impact of histological margins on recurrence for high-risk basal cell carcinomas and analysed the existence of a benefit of surgical revision in the case of inframillimetric margins.
Initial Management and Potential Opportunities to Deprescribe Dialysis among Patients with AKI-D Patients after Hospital Discharge
Authors: Ian E. McCoy, Eric Weinhandl, Wael Hussein, Chi-yuan Hsu
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement Dialysis-requiring AKI (AKI-D) now accounts for more than 15% of outpatient hemodialysis initiations; over 30% of these patients with AKI-D may have potential to recover. However, little is known about strategies currently used to treat outpatient AKI-D and screen for recovery. In this study of 1754 patients with AKI-D, we found that ( 1 ) the initial dialysis orders were similar to those of patients with contemporary incident ESKD, despite different treatment goals; ( 2 ) timed urine collections were completed in only a minority of patients; and ( 3 ) most patients with AKI-D who recovered discontinued dialysis without ever having been weaned from their initial dialysis prescription, suggesting there may be substantial opportunity to wean dialysis sooner.
Perception is iconic, perceptual working memory is discursive
Authors: Ned Block
Journal: Behavioral and Brain Sciences (2023)

Abstract The evidence that the target article cites for language-of-thought (LoT) structure in perceptual object representations concerns perceptual working memory, not perception. Perception is iconic, not structured like an LoT. Perceptual working memory representations contain the remnants of iconic perceptual representations, often recoded, in a discursive envelope.
Unlocking the Potential of Anti-TIGIT Therapy—Between Promise and Challenges
Authors: Joud Hajjar, Mohamed H. Derbala, Aung Naing
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Transcriptional Heterogeneity Overcomes Super-Enhancer Disrupting Drug Combinations in Multiple Myeloma
Authors: Seth J. Welsh, Benjamin G. Barwick, Erin W. Meermeier, Daniel L. Riggs, Chang-Xin Shi, Yuan Xiao Zhu, Meaghen E. Sharik, Megan T. Du, Leslie D. Abrego Rocha, Victoria M. Garbitt, Caleb K. Stein, Joachim L. Petit, Nathalie Meurice, Yuliza Tafoya Alvarado, Rodrigo Fonseca, Kennedi T. Todd, Sochilt Brown, Zachery J. Hammond, Nicklus H. Cuc, Courtney Wittenberg, Camille Herzog, Anna V. Roschke, Yulia N. Demchenko, Wei-dong D. Chen, Peng Li, Wei Liao, Warren J. Leonard, Sagar Lonial, Nizar J. Bahlis, Paola Neri, Lawrence H. Boise, Marta Chesi, P. Leif Bergsagel
Journal: Blood Cancer Discovery (2023)

Abstract Multiple myeloma (MM) is a malignancy that is often driven by MYC and that is sustained by IRF4, which are upregulated by super-enhancers. IKZF1 and IKZF3 bind to super-enhancers and can be degraded using immunomodulatory imide drugs (IMiD). Successful IMiD responses downregulate MYC and IRF4; however, this fails in IMiD-resistant cells. MYC and IRF4 downregulation can also be achieved in IMiD-resistant tumors using inhibitors of BET and EP300 transcriptional coactivator proteins; however, in vivo these drugs have a narrow therapeutic window. By combining IMiDs with EP300 inhibition, we demonstrate greater downregulation of MYC and IRF4, synergistic killing of myeloma in vitro and in vivo, and an increased therapeutic window. Interestingly, this potent combination failed where MYC and IRF4 expression was maintained by high levels of the AP-1 factor BATF. Our results identify an effective drug combination and a previously unrecognized mechanism of IMiD resistance. Significance: These results highlight the dependence of MM on IKZF1-bound super-enhancers, which can be effectively targeted by a potent therapeutic combination pairing IMiD-mediated degradation of IKZF1 and IKZF3 with EP300 inhibition. They also identify AP-1 factors as an unrecognized mechanism of IMiD resistance in MM. See related article by Neri, Barwick, et al., p. 56. See related commentary by Yun and Cleveland, p. 5. This article is featured in Selected Articles from This Issue, p. 4
Epigenetic Regulators Open the Door to SCLC Plasticity
Authors: Margaret C. Weber, Luke T. Izzo, Trudy G. Oliver
Journal: Cancer Research (2023)

Abstract Small-cell lung cancer (SCLC) is a neuroendocrine tumor type with limited treatment options and poor prognosis. SCLC comprises multiple molecular subtypes that are defined by the expression of the lineage-related transcription factors ASCL1, NEUROD1, POU2F3, and more controversially, YAP1. SCLC exhibits remarkable plasticity with the capacity to transition between molecular states; because these states are associated with unique therapeutic susceptibilities, SCLC has been likened to a moving therapeutic target. While MYC's role in driving the ASCL1-to-NEUROD1 (A-to-N) transition is established, additional mechanisms governing SCLC plasticity remain largely obscure. A recent study by Duplaquet and colleagues, published in Nature Cell Biology, employs an innovative genetically engineered mouse model of SCLC harboring loss of KDM6A—a histone lysine demethylase mutated in approximately 2% of SCLC cases. KDM6A loss in SCLC alters chromatin accessibility and increases the potential for A-to-N plasticity in vivo. Through characterization of the epigenetic landscape, Duplaquet and colleagues identified histone methylation as a key regulator of SCLC plasticity. These findings provide not only a new model system for studying SCLC plasticity, but also identify new epigenetic mechanisms involved, which will ultimately be critical for designing more effective therapies.
Venous Thromboembolism Chemoprophylaxis Adherence Rates After Major Cancer Surgery
Authors: Charles D. Logan, Matthew T. Hudnall, Cary Jo R. Schlick, Dustin D. French, Brian Bartle, Dominic Vitello, Hiten D. Patel, Lauren M. Woldanski, Daniel E. Abbott, Ryan P. Merkow, David D. Odell, David J. Bentrem
Journal: JAMA Network Open (2023)

Venous thromboembolism (VTE) represents a major source of preventable morbidity and mortality and is a leading cause of death in the US after cancer surgery. Previous research demonstrated variability in VTE chemoprophylaxis prescribing, although it is unknown how these rates compare with performance in the Veterans Health Administration (VHA).